Oxford Medical Case Reports, 2019;5, 199–201

doi: 10.1093/omcr/omz030 CASE REPORT

CASE REPORT Calcium crystal-associated mimicking a febrile systemic inflammatory disease in an elderly patient Anna Paula Duque Sousa1, Carlos Moura1, Priscila Ribeiro da Hora1 and Mittermayer Santiago1,2,3,*

1Service of of Santa Izabel Hospital, Praça Almeida Couto 500, 40050-405 Salvador, BA, Brazil, 2Department of Internal Medicine, Bahiana School of Medicine and Public Health, Avenida Dom João VI 275, Brotas, 40290-000 Salvador, BA, Brazil and 3Specialized Services in Rheumatology of Bahia, Rua Conde Filho 117, Graça, 40150-150 Salvador, BA, Brazil

*Correspondence address. Serviços Especializados em Reumatologia da Bahia, Rua Conde Filho, 117, Graça, CEP 40150-150 Salvador, Bahia, Brazil. Fax: (71) 30229886; E-mail: [email protected]

Abstract Crystal formation and deposition in the joints is an important and common cause of acute . The disease may present with fever and systemic signs. In this report, we describe the case of a 70-year-old man, who presented with a sudden and incapacitating polyarthritis of large and small joints, fever, asthenia and leukocytosis. After extensive investigation, radiography of the joints showed the presence of . A few days after the beginning of the treatment with colchicine, he became completely asymptomatic, drawing one’s attention of calcium crystal-associated arthropathy as a cause of febrile systemic inflammatory disease particularly in elderly population.

INTRODUCTION CASE REPORT Crystal formation and deposition of monosodium urate or A 70-year-old man was admitted to our hospital with fever and calcium pyrophosphate in the joints is an important and diffuse pain, mainly in cervical area and right shoulder initiated common cause of acute arthritis. In elderly, calcium pyrophos- 4 days before the admission. Soon after the hospitalization, phate dihydrate deposition disease (CPPD) is the leading cause he presented with polyarthritis in elbows, wrists, hands, knees of acute arthritis. The highest risk groups for CPPD, besides and ankles. Three weeks before the present hospitalization, he elderly, are individuals with , history of trauma, had a self-limited diarrhea secondary to rotavirus infection. He genetic and metabolic disturbances such as hemochromatosis, had no remarkable family history. At physical examination, the hyperparathyroidism and hypomagnesemia [1,2]. patient was bedridden because of pain. He had tachycardia, ◦ When the disease presents with fever and systemic signs, it fever (38 C) and evident polyarthritis in the right wrist, knees, can lead to a misdiagnosis and inappropriate treatment. elbows, shoulders, right ankle and right midfoot. The rest of Herein, we report the case of a patient with an atypical clin- the physical examination was unremarkable. Laboratory tests ical presentation of acute polyarthritis of large and small joints revealed hemoglobin of 14 mg/dL, total white blood count of associated with fever and systemic inflammatory symptoms 26.690 cells/mm3 with no shift deviation, erythrocyte sedimenta- secondary to a calcium crystal-associated disease. tion rate of 120 mm and c-reactive protein of 5.14 mg/dL (normal

Received: November 20, 2018. Revised: February 7, 2019. Accepted: February 24, 2019 © The Author(s) 2019. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]

199 200 A.P.D. Sousa et al.

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Figure 1: Radiographs showing chondrocalcinosis in meniscus of the knee, fibrocartilage of the wrist and elbow.

A regimen of 20 mg/day prednisone was initiated for symptomatic relief of the pain, with only partial improvement. Assuming a presumptive diagnosis of CCPD, colchicine 1 mg/day was started. The patient presented rapid improvement of his arthritis and fever within 48 h of the introduction of colchicine even with the suspension of the corticosteroids. He was discharged in use of colchicine, walking normally without fever and no other complaints.

DISCUSSION CPPD is a prevalent and important differential diagnosis of acute arthritis in the elderly [2,3]. The most common sites for crystal deposition are the fibrocartilages and hyaline cartilages (e.g. knee menisci, wrist triangular cartilage, hip and glenohumeral joint). Less commonly, CPP can be found in periarticular tissues as spinal ligaments and Achilles tendon [4]. When the crystals are formed, they can interact with plasma cell membrane, leading to activation of NLRP3 inflammasome- Figure 2: Radiograph of the right shoulder revealing joint space narrowing IL-1β pathway, the main mechanism of [5]. Once and irregularity of the glenohumeral bone surface compatible with ‘Milwaukee β shoulder’. released, IL-1 will lead to endothelial cells activation, neu- trophils recruitment and release of other inflammatory medi- ators, such as TNF-α, which may contribute for the development range up to 0.5 mg/dL). He had negative serology for dengue, B of arthritis and systemic manifestation of CPPD [6,7]. and C hepatitis, human immunodeficiency virus and syphilis. The acute form of the disease is characterized by sudden Urine culture was negative. Serum uric acid was within the nor- onset of , generally in elderly women, usually of mal range, and the patient had no history of hyperuricemia. The large joints, most commonly knees, wrists, shoulders or elbows. renal function (cretinine = 0.7 mg/dL; creatinine clearance esti- Acute attacks are self-limiting similar to what occurs in acute mate by Cockcroft–Gault = 104.17 mL/min), electrolytes (calcium, , which is the reason why CPPD has also been known as phosphorus and magnesium) as well as thyroid function and pseudogout [2]. On the other hand, sometimes, CPPD can present parathyroid hormone were normal. Transesophageal echocar- as polyarthritis, and it can be associated with systemic manifes- diography had no evidence of vegetation. Plane radiographs of tations such as fever, increased acute phase reactant levels and the joints demonstrated chondrocalcinosis in meniscus of the leukocytosis mimicking an infectious disease as was observed knees, fibrocartilage of the wrists, metacarpophalangeal joints in the present case [8–10]. Moreover, some case reports have and elbows articular cartilage (Fig. 1). The right shoulder had shown CPPD as a cause of altered mental status in elderly, which joint space narrowing and irregularity of the glenohumeral bone improved after treatment [9–11]. In this scenario, the presence surface resembling the one observed in the Milwaukee shoulder of infection should always be excluded due to its potential syndrome (Fig. 2). Unfortunately, we were not able to perform a morbidity. study to define the type of crystal present in his joints because Another febrile syndrome associated with crystal deposition polarized light microscopy for crystal search was not available in is called crowned dens syndrome, which is caused by the depo- this service. sition of crystal around the odontoid process. It manifests as Calcium crystal-associated arthropathy 201

recurrent attacks of fever, neck stiffness and is an important REFERENCES differential diagnosis with meningitis, spinal tumor or infectious 1. Ea HK, Liote F. Diagnosis and clinical manifestations spondylitis [12]. of calcium pyrophosphate and basic calcium phosphate The destructive arthropathy-type Milwaukee shoulder syn- crystal deposition diseases. Rheum Dis Clin North Am drome observed in our patient has been classically related to 2014;40:207–229. deposition of basic calcium phosphate (BCP) crystals, but it has 2. Ferrone C, Andracco R, Cimmino MA. Calcium pyrophos- also been described in association with CPPD [13,14]. In our case, phate deposition disease: clinical manifestations. Reuma- the presence of chondrocalcinosis in meniscus of the knees and tismo 2012;63:246–252. in the fibrocartilage of the wrist would corroborate the diagno- 3. Agudelo CA, Wise CM. Crystal-associated arthritis. Clin Geri- sis of CPPD. Moreover, to the best our knowledge, there is no atr Med 1998;14:495–513. description of polyarticular systemic form of BCP crystal deposi- 4. Doherty M, Dieppe P, Watt I. Pyrophosphate arthropathy: a tion. However, a study performed in cadavers demonstrated that prospective study. Br J Rheumatol 1993;32:189–196. radiological chondrocalcinosis is not specific for the chemical 5. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout- composition of the crystal as a high prevalence of BCP crystals associated uric acid crystals activate the NALP3 inflamma- was observed in joints with chondrocalcinosis [13]. Thus, we some. Nature 2006;440:237–241. cannot exclude the possibility of the presence of two types of crystals simultaneously in the joints of our patient [14]. 6. Busso N, Ea HK. The mechanisms of inflammation in Reumatismo The diagnosis of febrile CPPD polyarthritis in elderly largely gout and pseudogout (CPP-induced arthritis). relies on the examination, medical history and musculoskeletal 2012;63:230–237. exam by the attending physician in addition to joint aspiration 7. Abhishek A, Doherty M. Update on calcium pyrophosphate and search for crystals. A detailed study of the synovial fluid deposition. Clin Exp Rheumatol 2016;34:32–38. and the type of crystal in this clinical scenario is recommended 8. Mavrikakis ME, Antoniades LG, Kontoyannis SA, as part of the investigation of unexplained arthritis [15,16]. Not Moulopoulou DS, Papamichael CP, Kostopoulos CC et al. having performed a synovial fluid analysis is a limitation of our CPPD crystal deposition disease as a cause of unrecognised study. However, polarized light microscopy is available only in pyrexia. Clin Exp Rheumatol 1994;12:419–422. a few specialized laboratories in our region. In this particular 9. Masuda I, Ishikawa K. Clinical features of pseudogout case, it was an elderly patient that had acute polyarticular arthri- attack. A survey of 50 cases. Clin Orthop Relat Res 1988;229: tis and calcifications in fibrocartilage complex in wrists and 173–181. knees, suggesting calcium pyrophosphate deposition. Besides 10. Bong D, Bennett R. Pseudogout mimicking systemic disease. that, from the practical point of view, the therapeutic strategy JAMA 1981;246:1438–1440. is similar for both CPPD and BCP crystal deposition. Indeed, the 11. Kelley JT III, Agudelo CA, Sharma V, Holland NW. Fever good response to colchicine reinforces the diagnosis of disease with acute arthritis in calcium pyrophosphate dihydrate for deposition of crystals although not discriminating the type deposition disease: a missed explanation for altered men- of crystal. tal status in elderly patients? J Clin Rheumatol 2001;7: 322–325. 12. Godfrin-Valnet M, Godfrin G, Godard J, Prati C, Toussirot E, ACKNOWLEDGEMENTS Michel F et al. Eighteen cases of crowned dens syn- M.S. is currently receiving a scholarship from Conselho Nacional drome: presentation and diagnosis. Neurochirurgie 2013;59: de Desenvolvimento Científico e Tecnológico. 115–120. 13. Liote F, Ea HK. Clinical implications of pathogenic calcium crystals. Curr Opin Rheumatol 2014;26:192–196. CONFLICT OF INTEREST STATEMENT 14. Rosenthal AK, Ryan LM. Nonpharmacologic and pharmaco- None declared. logic management of CPP crystal arthritis and BCP arthropa- thy and periarticular syndromes. Rheum Dis Clin North Am 2014;40:343–356. ETHICAL APPROVAL 15. Landewe RB, Gunther KP, Lukas C, Braun J, Combe B, The case report did not require the ethical board approval. Conaghan PG et al. EULAR/EFORT recommendations for the diagnosis and initial management of patients with acute or recent onset swelling of the knee. Ann Rheum Dis CONSENT 2010;69:12–19. Consent has been obtained from the patient. 16. Zhang W, Doherty M, Bardin T, Barskova V, Guerne PA, Jansen TL et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. GUARANTOR Part I: terminology and diagnosis. Ann Rheum Dis 2011;70: Mittermayer Santiago is a guarantor of the article. 563–570.